Gut dysbiosis, endotoxemia and clotting activation: A dangerous trio for portal vein thrombosis in cirrhosis. (January 2023)

• Record Type: Journal Article
• Authors: Violi, Francesco; Pignatelli, Pasquale; Castellani, Valentina; Carnevale, Roberto; Cammisotto, Vittoria
• Is Part Of: Blood reviews. Volume 57(2023)
• Publication Date: 2023-01
• Subjects: Cirrhosis -- Coagulation -- Portal vein thrombosis -- Endotoxemia -- Platelet activation; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2022.100998
• Languages: English
• ISSNs: 0268-960X

Abstract

Abstract: Liver cirrhosis (LC) is associated with portal venous thrombosis (PVT) in roughly 20% of cirrhotic patients but the underlying mechanism is still unclear. Low-grade endotoxemia by lipopolysaccharides (LPS), a component of outer gut microbiota membrane, is detectable in the portal circulation of LC and could predispose to PVT. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction, that is a prerequisite for enhanced gut permeability and ensuing endotoxemia. Experimental and clinical studies provided evidence that LPS behaves a pro-thrombotic molecule so promoting clotting and platelet activation. Experiments conducted in the portal circulation of cirrhotic patients showed the existence of LPS-related enhanced thrombin generation as well as endothelial dysfunction, venous stasis, and platelet activation. The review will analyze 1) the pro-thrombotic role of endotoxemia in the context of LC 2) the biological plausibility linking endotoxemia with PVT and 3) the potentially interventional tools to lower endotoxemia and eventually hypercoagulation.